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Metabolic and hormonal side effects of mitotane treatment for adrenocortical carcinoma: A retrospective study in 50 Danish patients

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@article{b40153d9098c4d44b55f339c1a39dc45,
title = "Metabolic and hormonal side effects of mitotane treatment for adrenocortical carcinoma: A retrospective study in 50 Danish patients",
abstract = "OBJECTIVE: Mitotane is used in the treatment of adrenocortical carcinoma (ACC). Metabolic and hormonal side effects of mitotane, the effect of subsequent treatment with statins and hormones and the effects of discontinuation of mitotane were assessed.PATIENTS AND METHODS: Fifty patients were included. Lipid profiles, thyroid hormones, sex hormones and adrenal function from first year of mitotane treatment and after cessation were evaluated.RESULTS: After 6 months of mitotane treatment total cholesterol increased from (median) 5.1 (IQR 4.3 to 5.8) to 7.4 (6.2-9.0) mmol/L, p < .001. LDL, HDL and triglyceride also increased, all p ≤ .03. Three months of treatment with statins decreased total and LDL-cholesterol, and cessation of mitotane led to further reduction in lipids. Plasma thyroxine decreased from 90 (78-111) to 57 (47-63) nmol/L and free thyroxine from 16.0 (13.0-18.3) to 11.7 (10.5-12.6) pmol/L on mitotane, both p < .001, while TSH remained unchanged. Treatment with thyroxin significantly increased plasma thyroxine and free thyroxine and decreased TSH. Cessation of mitotane increased total T4 (p < .001). Mitotane increased plasma SHBG from 36 (22-51) to 189 (85-259) nmol/L and LH from 4.6 (1.6-8.1) to 20.0 (10.0-34.9) IU/L, both p < .001. In males the changes were accompanied by an increase in testosterone from 9.8 (7.2-14.5) to 27.0 (15.3-34.8) nmol/L, p < .03. Fifteen of 24 tested patients regained normal adrenal function 6 (3-16) months after cessation of mitotane.CONCLUSIONS: Mitotane treatment exerts multiple severe side effects involving both the metabolic and endocrine systems that may require treatment, but the effect appears to be partially reversible.",
keywords = "adrenocortical carcinoma, hypercholesterolemia, hypergonadotropic hypogonadism, hypothyroidism, mitotane treatment",
author = "Vikner, {Malene Elbaek} and Jesper Krogh and Gedske Daugaard and Mikkel Andreassen",
note = "{\textcopyright} 2020 John Wiley & Sons Ltd.",
year = "2021",
month = feb,
doi = "10.1111/cen.14345",
language = "English",
volume = "94",
pages = "141--149",
journal = "Clinical Endocrinology",
issn = "0300-0664",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "2",

}

RIS

TY - JOUR

T1 - Metabolic and hormonal side effects of mitotane treatment for adrenocortical carcinoma

T2 - A retrospective study in 50 Danish patients

AU - Vikner, Malene Elbaek

AU - Krogh, Jesper

AU - Daugaard, Gedske

AU - Andreassen, Mikkel

N1 - © 2020 John Wiley & Sons Ltd.

PY - 2021/2

Y1 - 2021/2

N2 - OBJECTIVE: Mitotane is used in the treatment of adrenocortical carcinoma (ACC). Metabolic and hormonal side effects of mitotane, the effect of subsequent treatment with statins and hormones and the effects of discontinuation of mitotane were assessed.PATIENTS AND METHODS: Fifty patients were included. Lipid profiles, thyroid hormones, sex hormones and adrenal function from first year of mitotane treatment and after cessation were evaluated.RESULTS: After 6 months of mitotane treatment total cholesterol increased from (median) 5.1 (IQR 4.3 to 5.8) to 7.4 (6.2-9.0) mmol/L, p < .001. LDL, HDL and triglyceride also increased, all p ≤ .03. Three months of treatment with statins decreased total and LDL-cholesterol, and cessation of mitotane led to further reduction in lipids. Plasma thyroxine decreased from 90 (78-111) to 57 (47-63) nmol/L and free thyroxine from 16.0 (13.0-18.3) to 11.7 (10.5-12.6) pmol/L on mitotane, both p < .001, while TSH remained unchanged. Treatment with thyroxin significantly increased plasma thyroxine and free thyroxine and decreased TSH. Cessation of mitotane increased total T4 (p < .001). Mitotane increased plasma SHBG from 36 (22-51) to 189 (85-259) nmol/L and LH from 4.6 (1.6-8.1) to 20.0 (10.0-34.9) IU/L, both p < .001. In males the changes were accompanied by an increase in testosterone from 9.8 (7.2-14.5) to 27.0 (15.3-34.8) nmol/L, p < .03. Fifteen of 24 tested patients regained normal adrenal function 6 (3-16) months after cessation of mitotane.CONCLUSIONS: Mitotane treatment exerts multiple severe side effects involving both the metabolic and endocrine systems that may require treatment, but the effect appears to be partially reversible.

AB - OBJECTIVE: Mitotane is used in the treatment of adrenocortical carcinoma (ACC). Metabolic and hormonal side effects of mitotane, the effect of subsequent treatment with statins and hormones and the effects of discontinuation of mitotane were assessed.PATIENTS AND METHODS: Fifty patients were included. Lipid profiles, thyroid hormones, sex hormones and adrenal function from first year of mitotane treatment and after cessation were evaluated.RESULTS: After 6 months of mitotane treatment total cholesterol increased from (median) 5.1 (IQR 4.3 to 5.8) to 7.4 (6.2-9.0) mmol/L, p < .001. LDL, HDL and triglyceride also increased, all p ≤ .03. Three months of treatment with statins decreased total and LDL-cholesterol, and cessation of mitotane led to further reduction in lipids. Plasma thyroxine decreased from 90 (78-111) to 57 (47-63) nmol/L and free thyroxine from 16.0 (13.0-18.3) to 11.7 (10.5-12.6) pmol/L on mitotane, both p < .001, while TSH remained unchanged. Treatment with thyroxin significantly increased plasma thyroxine and free thyroxine and decreased TSH. Cessation of mitotane increased total T4 (p < .001). Mitotane increased plasma SHBG from 36 (22-51) to 189 (85-259) nmol/L and LH from 4.6 (1.6-8.1) to 20.0 (10.0-34.9) IU/L, both p < .001. In males the changes were accompanied by an increase in testosterone from 9.8 (7.2-14.5) to 27.0 (15.3-34.8) nmol/L, p < .03. Fifteen of 24 tested patients regained normal adrenal function 6 (3-16) months after cessation of mitotane.CONCLUSIONS: Mitotane treatment exerts multiple severe side effects involving both the metabolic and endocrine systems that may require treatment, but the effect appears to be partially reversible.

KW - adrenocortical carcinoma

KW - hypercholesterolemia

KW - hypergonadotropic hypogonadism

KW - hypothyroidism

KW - mitotane treatment

UR - http://www.scopus.com/inward/record.url?scp=85092596100&partnerID=8YFLogxK

U2 - 10.1111/cen.14345

DO - 10.1111/cen.14345

M3 - Journal article

C2 - 32996176

VL - 94

SP - 141

EP - 149

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 2

ER -

ID: 61373095